Genetic Variation of Muscle Mass Adequate skeletal muscle mass is an essential component of an individual's health and a predictor of quality of life. Decrease in muscle mass and its ability to generate force is a prominent feature of various myopathies. Genetic factors play an important role in determining skeletal muscle mass. The LG/J and SM/J mouse strains have been selected for large and small body weight, respectively, at 60 days of age and it is plausible that selection would have had a major impact on muscle mass (a key component of body weight). We propose to explore the genetic architecture underlying variation in muscle weight of mice from the LG/SM lineage and to nominate candidate genes underlying the variability. We will map quantitative trait loci (QTL) in five hind limb muscles of an F2 intercross between the LG/J and SM/J strains (LGSMF2), then we refine their location in mice of the 34th generation (LGSMF34) of advanced intercross lines (AIL) of these strains. Congenic strains will be generated for verification of QTL and as a resource for further exploration of the biological mechanisms relevant to each locus. We will utilize bioinformatics tools to nominate candidate genes when the confidence intervals for each locus has been reduced by the AIL/congenic mapping strategy. Elucidation of the genetic architecture will lead to identification of biological pathways governing muscle development and/or maintenance, which can be used as pharmaceutical targets for prevention of muscle loss due to inactivity or disease. PUBLIC HEALTH RELEVANCE: Genetic mechanisms influencing variability in muscle mass are incompletely understood. To shed light on the genetic factors affecting skeletal muscle, we will study the genetic architecture underlying variation in muscle weight between two mouse strains; one selected for high another for low body weight. The effort will lead to the biological pathways that may be targeted to prevent muscle loss due to aging or disease in humans.